Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With Low or Low-Normal Testosterone Levels

Abstract

Background: Serum testosterone levels and insulin sensitivity both decrease with age. Severe testosterone deficiency is associated with the development of insulin resistance. However, the effects of long-term testosterone administration on insulin sensitivity in older men with low or low-normal testosterone levels remain unknown.

Methods: The Testosterone Effects on Atherosclerosis in Aging Men Trial was a placebo-controlled, randomized, double-blind trial. The participants were 308 community-dwelling men, ≥60 years old, with total testosterone 100 to 400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean age, 66.7 ± 5.1 years) underwent an octreotide insulin suppression test at baseline and at 3 and 36 months after randomization to measure insulin sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose (SSPG) concentration at equilibrium during octreotide and insulin administration. Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by dual energy x-ray absorptiometry.

Results: There was a significant (P = 0.003) increase in SSPG in the placebo group, whereas no change was seen in testosterone-treated subjects from baseline to 36 months; however, the between-group differences in change in SSPG over 3 years were not statistically significant (+15.3 ± 6.9 mg/dL in the placebo group vs +6.2 ± 6.4 mg/dL in the testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with testosterone treatment were not associated with changes in serum total or free testosterone concentrations. Changes in TFM but not TLM were associated with increases in SSPG. Stratification by age or baseline total testosterone level did not show significant intervention effects.

Conclusion: Testosterone administration for 36 months in older men with low or low-normal testosterone levels did not improve insulin sensitivity.

Trial registration: ClinicalTrials.gov NCT00287586.

Figures

Figure 1.

Change in insulin sensitivity over time measured by the OIST and estimated as the mean concentration of glucose at equilibrium SSPG by averaging the values during the last 30 minutes of the infusion at the 160-, 170-, and 180-minute time points.P values were extracted from mixed-model regression.

Figure 2.

Scatter plot of association between change from baseline in insulin sensitivity estimated as SSPG from the OIST, with changes in (A and B) serum testosterone concentrations and (C and D) body composition at 36 months in testosterone-treated men (n = 74). P value and R2 were extracted from a simple linear regression model.

Figure 3.

Forest plot of estimated changes from baseline at 36 months between testosterone and placebo groups stratified by baseline total testosterone levels ≤300 ng/dL and >300 ng/dL and by age ≤75 years and >75 years. P values were extracted from mixed-model regression.